BPA may influence neurodevelopmental disorders

BPA may have a part in the development of disorders such as Rett syndrome

BPA, a molecule that mimics estrogen and interferes with the body's endocrine system, can be found in a wide variety of manufactured products including medical devices, compact discs, dental sealants, water bottles, the lining of canned foods and drinks, and more. The chemical can be ingested if it seeps into the contents of food and beverage containers. More than 90 percent of us have BPA in our bodies due to food containers made with BPA but it is also possible to be exposed to BPA through air, dust and water.

More than 200 lab animal tests to date strongly suggest that BPA exposure, even at very low doses, creates risks of dangerous developmental, neural and reproductive health effects in adults, children and infants. In 2012, the US Food and Drug Administration (FDA) announced that BPA will no longer be allowed in baby bottles and sippy cups but does not apply to other plastics or food packaging, which included cans and baby formula.

BPA is a universal compound that is rising as a possible toxicant during embryonic development. BPA has been shown to epigenetically affect the developing nervous system, but the molecular mechanisms are not clear. This led the researchers from Duke University School of Medicine to develop a series of experiments in rodent and human nerve cells to determine how BPA influences changes that disrupt gene regulation (a process in which a cell determines which genes it will express and when).

During early development of neurons, high levels of chloride are present in cells. These levels drop as neurons mature, thanks to a chloride transporter protein called KCC2, which agitates chloride ions out of the cells. If the level of chloride within neurons remains elevated, it can damage neural circuits and compromise a developing nerve cell's ability to migrate to its proper position in the brain.

Exposing neurons to minute amounts of BPA alters the chloride levels inside the cells by somehow shutting down the Kcc2 gene, which makes the KCC2 protein, thereby delaying the removal of chloride from neurons.

MECP2, another protein (that appears to be essential for the normal function of nerve cells) and was found to be the possible culprit behind this change. When exposed to BPA, MECP2 is more abundant and binds to the Kcc2 gene at a higher rate, which might help to shut it down. This could add to problems in the developing brain due to a delay in chloride being removed.

While both male and female neurons were affected by BPA in the studies, female neurons were more susceptible to the chemical's toxicity. Further research will dig deeper into the sex-specific effects of BPA exposure and whether certain sex hormone receptors are involved in BPA's effect on KCC2.

The research team writes “Overall, our results indicate that BPA can disrupt Kcc2 gene expression through epigenetic mechanisms. Beyond increase in basic understanding, our findings have relevance for identifying unique neurodevelopmental toxicity mechanisms of BPA, which could possibly play a role in pathogenesis of human neurodevelopmental disorders.”

These findings bring up the question if BPA could add to neurodevelopmental disorders such as Rett syndrome, the most physically disabling of the autism spectrum disorders that strikes at random in early childhood affecting little girls almost exclusively and is distinguished by mutations in the gene that produces MECP2.

Dr. Wolfgang Liedtke, MD, PHD, Center for Translational Neuroscience, Assistant Professor/Head of Laboratory, Duke University Medical Center and lead author of study commented in a news release from Duke "Our study found that BPA may impair the development of the central nervous system, and raises the question as to whether exposure could predispose animals and humans to neurodevelopmental disorders.”

In closing Dr. Liedtke commented "Our findings improve our understanding of how environmental exposure to BPA can affect the regulation of the Kcc2 gene. However, we expect future studies to focus on what targets aside from Kcc2 are affected by BPA.” "This is a chapter in an ongoing story."

This study appears in the journal Proceedings of the National Academy of Sciences.

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